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Journal of Lipid Research, Vol. 50, S207-S212, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Oxidized Lipids

The role of oxidized phospholipids in atherosclerosis

Judith A. Berliner^1,*, Norbert Leitinger and Sotirios Tsimikas

^* Departments of Pathology and Medicine, University of California, Los Angeles, CA
Department of Pharmacology and the Robert Berne Center for Cardiovascular Research, University of Virginia, Charlottesville, VA
Department of Medicine, University of California, San Diego, CA

This work was supported by National Institutes of Health Grants P01 HL30568 (J.B.), R01 HL064731 (J.B.), and R01 HL084422 (N.L.), by the American Heart Association (N.L.), and by The Fondation Leducq (S.T.).

Published, JLR Papers in Press, December 4, 2008.

¹ To whom correspondence should be address. e-mail: jberliner{at}mednet.ucla.edu

ABSTRACT

There is increasing evidence that oxidized phospholipids (OxPLs) play an important role in atherosclerosis. These phospholipids accumulate in human and mouse lesions. Specific OxPLs have been identified as major regulators of many cell types present in the vessel wall. In endothelial cells, >1,000 genes are regulated. Some of these genes are pro-atherogenic and others anti-atherogenic. The anti-atherogenic effects are likely important in slowing the atherogenic process. Several receptors and signaling pathways associated with OxPL action have been identified and shown to be upregulated in human lesions. A structural model of the mechanism by which specific OxPLs serve as CD36 ligands has been identified. Specific oxidized phospholipids are also present in plasma and associated with Lp(a) particles. In humans, OxPL/apolipoprotein B has been shown to be a prognostic indicator and a separate risk factor for coronary events. Levels of OxPL in plasma have been shown to be correlated with platelet activation. The results of these studies suggest an important role for OxPL in all stages of atherosclerosis.

Supplementary key words endothelial • macrophage • smooth muscle cells • clinical trials

Abbreviations: apoB, apolipoprotein B; apoE, apolipoprotein E; DC, dendritic cell; KOdiA-PC, 9-keto-10-dodecendioic acid ester of 2-lyso-phosphatidyl choline; Lp(a), lipoprotein (a); OxPL, oxidized phospholipid; PAPC, palmitoyl arachidonyl phosphatidyl choline; PGJ2, 15 deoxy-delta12,14 prostaglandin J2; PEIPC, 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphoryl choline; SMC, smooth muscle cell

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